This project is concerned with the role of the central catecholamines in positive reinforcement produced by brain stimulation in the rat. The principal advantage of the approach proposed is that it is based on the ability of neural tissue to regenerate after injury to produce hyperinnervation of a given region. Specifically, with respect to the norepinephrine-containing neurons of the pontine region it is possible to induce through neonatal injury changes that produce an elevation of norepinephrine concentration in this region and hyperinnervation. With this preparation as a model of an identified transmitter-enriched region, it becomes feasible to ask whether the positive reinforcement associated with this region is altered. Previously we showed that rats which had telencephalic catecholamines depleted but mesencephalic levels nearly normal after treatment during adulthood with 6-hydroxydopamine (6-OHDA) stopped responding for the brain reward at the depleted sites but not at the nondepleted ones. More recently, we showed that norepinephrine levels in the pontine region of the rat brain permanently raised through neonatal treatment with 6-OHDA led to hyper-reward in that region and to hypo-reward in the depleted medial forebrain bundle region. Experiments are proposed which are designed to investigate, with the use of anatomical and physiological methods, the basis for the hyper-reward in the pontine region and to determine whether this phenomenon can also be obtained in other regions giving rise to ascending catecholaminergic projections and support positive reinforcement with brain stimulation.